Adrenomedullin was discovered in 1993 as a peptide involved in regulation of the circulatory system with strong vasodilatory effects (Patent Document 1). Adrenomedullin is produced by a variety of organs such as those of the circulatory system and the digestive system, and has important physiological effects such as vasodilatation, neovascularization, antibacterial effects, anti-enteritic effects, protection of the gastric mucosa, and suppression of thrombus formation. Administration of adrenomedullin has correspondingly been confirmed to be effective in the treatment of various diseases, and has been reported to be effective against conditions including myocardial disorders, non-bacterial inflammatory diseases, pulmonary hypertension, bone disorders, myometrial contraction, urinary disorders, and the like (Patent Documents 2 to 7).
However, since adrenomedullin is a peptide, formulation of it is associated with high costs of production, and in the case of direct administration of adrenomedullin, a dosage form such as an injectable preparation or an intravenous drip preparation must be used. Rigorous production technology and management excluding incorporation of foreign matter, such as endotoxin, is thus required. Furthermore, since adrenomedullin has a half-life in blood of only tens of minutes, administration of significant amounts is required for exertion of its effects. However, intravenous administration of a large amount of adrenomedullin may induce hypotension. Moreover, when exposure of specific organs to adrenomedullin is expected, various problems may exist, such as the need for targeting technologies. There has thus been a need for a highly safe medicament which can be produced at low cost and that is when orally administered capable of enhancing activity of the adrenomedullin production system, which is constitutively activated in vivo. However, no such medicament has been available.
Patent Document 1: Japanese Patent No. 2774769
Patent Document 2: WO 00/078338
Patent Document 3: WO 00/078339
Patent Document 4: JP-T-2002-540216
Patent Document 5: JP-A-2003-300899
Patent Document 6: JP-A-2006-290777
Patent Document 7: JP-A-2006-290814